title: Improved glycemic control enhances the incretin effect in patients with type 2 diabetes.
abstract: OBJECTIVE
  Impairment of the incretin effect is one of the hallmarks of type 2 diabetes mellitus (T2DM). However, it is unknown whether this abnormality is specific to incretin-stimulated insulin secretion or a manifestation of generalized β-cell dysfunction. The aim of this study was to determine whether improved glycemic control restores the incretin effect.
  
  
  METHODS
  Fifteen T2DM subjects were studied before and after 8 weeks of intensified treatment with insulin. The incretin effect was determined by comparing plasma insulin and C-peptide levels at clamped hyperglycemia from iv glucose, and iv glucose plus glucose ingestion.
  
  
  RESULTS
  Long-acting insulin, titrated to reduce fasting glucose to 7 mM, lowered hemoglobin A1c from 8.6% ± 0.2% to 7.1% ± 0.2% over 8 weeks. The incremental C-peptide responses and insulin secretion rates to iv glucose did not differ before and after insulin treatment (5.6 ± 1.0 and 6.0 ± 0.9 nmol/L·min and 0.75 ± 0.10 and 0.76 ± 0.11 pmol/min), but the C-peptide response to glucose ingestion was greater after treatment than before (10.9 ± 2.2 and 7.1 ± 0.9 nmol/L·min; P = .03) as were the insulin secretion rates (1.11 ± 0.22 and 0.67 ± 0.07 pmol/min; P = .04). The incretin effect computed from plasma C-peptide was 21.8% ± 6.5% before insulin treatment and increased 40.9% ± 3.9% after insulin treatment (P < .02).
  
  
  CONCLUSIONS
  Intensified insulin treatment to improve glycemic control led to a disproportionate improvement of insulin secretion in response to oral compared with iv glucose stimulation in patients with type 2 diabetes. This suggests that in T2DM the impaired incretin effect is independent of abnormal glucose-stimulated insulin secretion.
authors.affiliation: MD, 2170 East Galbraith Road, Room E-319, University of Cincinnati, Cincinnati, OH 45237. dalessd@ucmail.uc.edu.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: An
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Prigeon
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
mesh_terms: D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016903:Drug Monitoring; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D054795:Incretins / Q000097:blood* / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000069036:Insulin Glargine; D007333:Insulin Resistance; D000078790:Insulin Secretion; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine